Migraine is a recurrent clinical syndrome characterised by combinations of neurological, gastrointestinal and autonomic manifestations. The exact patho-physiological disturbances that occur with migraine have yet to be elucidated; however, cervico-trigemino-vascular dysfunctions appear to be the primary cause.

Despite advances in the understanding of the pathophysiology of migraine and new effective treatment options, migraine remains an under-diagnosed, under-treated and poorly treated health condition. Most patients will unsuccessfully attempt to treat their headaches with over-the-counter medications.

Few well designed, placebo-controlled studies are available to guide physicians in medication selection. Recently published evidence-based guidelines advocate migraine-specific drugs, such as serotonin 5-HT1b/1d agonists (the ‘triptans’) and dihydroergotamine mesylate, for patients experiencing moderate to severe migraine attacks. Additional headache attack therapy options include other ergotamine derivatives, phenothiazines, nonsteroidal anti-inflammatory agents and opioids.

Many women experience headaches, including migraine, in association with their menstrual cycles. Although definitions vary, menstrual migraine generally refers to migraine without aura that occurs within several days prior to and several days after the onset of menses.

Although menstrual migraine has been reported to be more difficult to treat than other types of migraines, there is no evidence from controlled clinical trials to support this assertion. Thus, the pharmacological treatment of menstrual migraine should be similar to that of other types of migraines, except with respect to the use of hormonal manipulations to treat menstrual migraine.

Serotonin 5-HT1B/1D receptor agonists (triptans) are effective for the acute treatment of both menstrual and non-menstrual migraines. When used as acute therapy, a triptan should be administered early, when the headache is still mild in severity. Ideally, an acute therapy will provide rapid and complete pain relief with no disability. Some patients may require preventive therapy for menstrual migraine based on suboptimal response to an adequate trial of acute therapy. Patient diaries that record headache onset, relationship to the menstrual cycle and treatment response through three complete cycles will allow accurate prediction of the onset of menstrual migraine; this information is also needed to make decisions about timing of intermittent preventive therapy. The goals of intermittent preventive therapy are to reduce the frequency, duration and intensity of menstrual migraine attacks.

Clinical studies show that triptans are effective when used as either acute therapy or as intermittent preventive therapy for menstrual migraine. Sumatriptan and zolmitriptan have been evaluated in prospective, randomised, controlled trials for acute treatment. Retrospective analyses and open-label studies also support the use of other triptans as acute therapy. In addition, sumatriptan, frovatriptan, naratriptan and zolmitriptan have been evaluated as intermittent preventive therapy in prospective studies. Thus, data from clinical studies indicate that triptans are effective for the treatment of menstrual migraine.

Migraine is a common neurological disease affecting about 12% of the population in Western Europe and North America, and causing a considerable burden both to migraineurs and to society. Severe, frequent and disabling migraine attacks, as well as those poorly responsive to acute care medication, require preventive treatment, which is often under-utilized. Antiepileptic drugs are used in the prevention of migraine.

We performed a literature search of PubMed through June 2008 for controlled trials of antiepileptic drugs in the prevention of migraine. The search identified 70 papers for a full-text review. The majority of these papers referred to valproate and topiramate, and showed that these drugs are effective and well tolerated in migraine prevention and are suitable for first-line clinical use. On the other hand, acetazolamide, lamotrigine, oxcarbazepine and vigabatrin have been shown to be not effective and gabapentin requires further evaluation. For the rest of the antiepileptic drugs, no data from controlled trials are available.

Migraine is a common disabling neurological disorder resulting from excessive cortical excitation and trigeminovascular afferent sensitization. In addition to aberrant neuronal processing, migraineurs are also at significant risk of vascular disease. Consequently, the impact of migraine extends well beyond the ictal headache and includes a well-documented association with acute ischemic stroke, particularly in young women with a history of migraine with aura. The association between migraine and stroke has been acknowledged for 40 years or more. However, examining the pathobiology of this association has become a more recent and critically important undertaking. The diversity of mechanisms underlying the association between migraine and stroke likely reflects the heterogenous nature of this disorder. Vasospasm, endothelial injury, platelet aggregation and prothrombotic states, cortical spreading depression, carotid dissection, genetic variants, and traditional vascular risk factors have been offered as putative mechanisms involved in migraine-related stroke risk. Assimilating these seemingly divergent pathomechanisms into a cogent understanding of migraine-related stroke will inform future studies and the development of new strategies for the prevention and treatment of migraine and stroke.

Epidemiological data suggest a link between migraine and the female sex hormones. Indeed, it is known that estrogen affects various brain functions, including pain perception. The prevalence of migraine is similar in boys and girls before puberty, but is 3-fold higher in postpubertal females compared with males. Migraine attacks in women are more likely to occur in the perimenstrual period and occur exclusively so in some women. The acute treatment of menstrual migraine is similar to that of non-menstrually related attacks, but the response to treatment may be less favourable. Perimenstrual prophylaxis, with NSAIDs, triptans or estradiol, is effective in decreasing attack frequency and severity.

The use of oral contraceptives (OCs) may change migraine frequency and severity. Since both migraine and hormonal contraceptive use are risk factors for ischaemic stroke, the use of OCs in women who experience migraine should be made only after consideration of the benefit-risk ratio.

Migraine typically, but not invariably, improves during the last two trimesters of pregnancy, and may worsen in the postpartum period. When using drugs to treat migraine during pregnancy, potential risks to the mother and fetus should be considered.

The prevalence of migraine decreases with advancing age and it improves in many, but not all, women after the menopause. However, in the perimenopausal period, migraine may worsen as a result of fluctuations in estrogen levels. Reducing the estrogen dose and changing the estrogen type or the route of administration of hormone replacement therapy (HRT) from oral to transdermal may reduce headache. Migraine is not a risk factor for stroke in postmenopausal women. When considering symptomatic HRT for postmenopausal migraneurs, the usual indications and contraindications should be applied. HRT may also exacerbate migraine.

Headaches are common disorders and migraine is most intensively investigated due to its high prevalence and often highly disabling character. Many conditions that are likewise prevalent have been described comorbid with migraine, and an increase of many comorbid conditions is seen among those with migraine with aura and higher frequency of headache. Well-established comorbidities include cardiovascular, psychiatric, neurological, and other pain disorders. With regard to cardiovascular disorders an association between migraine with aura and ischemic stroke has been most consistently described. Migraine with aura confers a twofold increased risk. Younger age, female gender, smoking, and oral contraceptive use seem to further raise the risk among migraineurs. With regard to psychiatric disorders, those with migraine are at increased risk of major depression, anxiety, panic disorder, bipolar disorder, abuse and neglect, and suicidal ideation or attempts. Common neurologic comorbidities include epilepsy and restless leg syndrome. Potential explanations for increased comorbidities will be explored. The complex network of an association between migraine and many other comorbid conditions is likely due to shared genetic factors that are further modified by environmental factors.

The primary headaches carry a substantial hereditary liability, as shown by twin and family studies. Hereditary factors account for an important proportion of the phenotypic variance in migraine with aura (MA) and without aura (MO) and tension-type headache (TTH), while the disease risk is also considerably increased for first-degree relatives of cluster headache (CH) patients. The patterns of inheritance are complex, which means that both genetic and environmental factors contribute. Familial hemiplegic migraine (FHM), a monogenic subtype of MA, has an autosomal dominant pattern of inheritance, and so far can be ascribed to mutations in three genes, CACNA1A, ATP1A2, and SCN1A, all coding for ion channels. Available studies have not provided clear evidence that these genes are also involved in the more common forms of migraine (MA and MO). Genome-wide linkage studies and genetic association studies based on candidate genes, but no genome-wide association studies, have been performed in migraine, leading to the discovery of several chromosomal loci. Underlying genes, however, have yet to be discovered. This also applies to studies in TTH and CH. Current research tackles methodological flaws in former studies by using large patient cohorts, multivariate statistical methods, and reducing clinical heterogeneity by the introduction of more refined methods of phenotyping, such as latent class analysis and trait component analysis. Also, gene expression profiles by detecting reliable biomarkers of disease will be helpful in the future. Results of large genome-wide association studies for migraine are expected soon. Future fields of headache research pertain to individual response and adverse effects to therapeutic drugs (pharmacogenetics), and the study of epigenetic factors.

Ophthalmologists and neurologists frequently see patients who complain of transient neurologic phenomena, most of which are visual, that are associated with a headache. The differentiation of migraine episodes from seizures and the vaso-occlusive disorders is not always immediately obvious, but an awareness of the types of migraines, migrainous phenomena, and migraine complications will help in formulating the appropriate clinical diagnosis. Migraine cannot be understood without knowledge of the normal ocular and cerebral blood flow and the factors that alter these circulations. A single approach to treatment of every case is not possible, but drugs or other therapies that modify or reverse these changes can be used to outline a rational plan of therapy.

Assessing the risk of stroke in persons with migraine is complicated by the intricate relationship between these two conditions. Both migraine and stroke are common and co-morbidity may, in some cases, be coincidental. Given the overlap of clinical symptoms in stroke and migraine, each condition may also mimic the other. Numerous studies have, however, shown that migraine is an independent risk factor for stroke both during, and remote from, the migraine attack. Women of childbearing age and those with aura are at greatest risk of migraine-related stroke. Additional risk of stroke in migraineurs occurs in those using oral contraceptive pills and who smoke cigarettes. Elevated blood pressure, an important stroke risk factor, is less common in migraineurs. Acquired antiphospholipid antibodies, not clearly a cause of migraine per se, may raise the risk of infarction in migraineurs. Hereditary conditions, including CADASIL (cerebral autosomal dominant arteriopathy with sub-cortical infarcts and leukoencephalopathy), MELAS (mitochondrial myopathy, encephalopathy, lactacidosis and stroke) and hereditary haemorrhagic telangiectasia, appear to predispose to both migraine and stroke. Purported mechanisms for migraine-associated stroke include involvement of the vasculature (including vasospasm, arterial dissection and small vessel arteriopathy), hypercoagulability (elevated von Willebrand Factor, platelet activation) and elevated risk of cardioembolism (patent foramen ovale, atrial septal aneurysm). Triptans and ergotamines, used to treat acute migraine attacks, appear to be safe in low-risk populations. These medications should be avoided in persons with haemiplegic migraine, basilar migraine, vascular risk factor and prior cerebral or cardiac ischaemia.